P780: G-CSF THERAPY IN EUROPEAN PATIENTS WITH SHWACHMAN-DIAMOND SYNDROME
Authors: Sabine Mellor-Heineke, Julia Skokowa, Natali Gerschmann, Ekatharina Deordieva, Anna Schsherbina, Ivan Tesakov, Karl Welte, Cornelia Zeidler
Journal: HemaSphere (2023)

Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical Background: Shwachman- Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by bone marrow failure (BMF), exocrine pancreatic dysfunction, and a varying degree of congenital abnormalities including the skeleton, liver, heart and immune system. Neutropenia is the most common hematological finding. SDS patients have a predisposition to myeloid malignancies and an increased risk for severe cytopenias. G-CSF therapy in SDS patients has always been discussed controversially. Parents and doctors are afraid to induce secondary myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in SDS patients by G-CSF treatment. Aims: Here we report on the safety and effectiveness of G-CSF therapy in our cohort of SDS patients. Methods: We have analyzed data on 176 European patients with the clinical diagnosis of Shwachman- Diamond Syndrome (SDS) collected by Severe Chronic Neutropenia International Registry (SCNIR). Results: Patient characteristics: 176 SDS patients (85 female, 91 male) with a median age at last follow up of 9.59 years (range 0.95 – 45.54 years). 141 patients are alive, 11 patients are expired, 23 patients are lost to follow-up. Causes of death were MDS/AML (n=4), transplant related mortality (n=5), infection (n=2). The median age at clinical SDS diagnosis is 1.75 years (range 0 -23.62 years). Mutations in the SBDS gene were detected in 90% of patients with the majority of patients (67%) harboring the common compound heterozygous mutations 258 + 2T>C + 183_184TA>CT. Overall, G-CSF therapy was given to 62 of 176 of patients (35%) either short term (< 1year), long term (>1 year) or only interventional (e.g. during infections). Complete data on G-CSF therapy and course of CBCs before and on therapy was available in 121 patients. Therefore, our analysis focusses on this cohort of 121 patients. In the first reported CBC 88 patients showed neutropenia with an absolute neutrophil count (ANC) below 1500/µl. 39 of 121 received G-CSF therapy: interventional in 2, less than 1 year in 8 and long term (>1 year) in 25 patients. The duration was not reported in 4 patients. In the long-term G-CSF group the median age at start of therapy was 2.45 years (0.05 - 21.97 years) with a median dose of 2.0 µg/kg/day (0.3-5 µg/kg/day) and a median duration of 2.7 years (1.00- 13.6 years). All patients showed an increase in the ANC with the initiation of therapy. No patient was reported to be a non-responder to G-CSF therapy. In the cohort of 121 SDS patients 11 patients were reported to develop MDS/AML. Only 2 patients were on long term G-CSF therapy at the time of MDS/AML diagnosis. Summary/Conclusion: Only a third of SDS patients received G-CSF therapy despite more patients being neutropenic. All patients treated had a good response to G-CSF therapy with an increase in their ANCs Only small daily doses were needed to reach this goal. The majority of SDS patients who developed MDS/AML were not on G-CSF therapy at the time of MDS/AML diagnosis. Keywords: G-CSF, Neutropenia, Bone marrow failure